Dahl salt-sensitive rats (SS) exhibit defects in the regulation of their renin-angiotensin system (RAS) that result in chronically low plasma renin activity (PRA) and low circulating ANG " levels, even when they are normotensive and fed a normal salt (NS) diet (0.4% NaCI). Normotensive SS rats fed NS diet also exhibit an impaired response to vasodilator stimuli, which is strikingly similar to the endothelial dysfunction that has been show to be a predictor of adverse cardiovascular events, including death, in humans. This project will test the hypothesis that exposure to chronically low plasma ANG " levels occurring as a result of defective regulation of the RAS in rats carrying the SS renin allele leads to impaired vascular relaxation. Recently, novel narrowed congenic rat strains have been developed that carry either the SS renin allele (impaired RAS regulation) or the Brown Norway (BN) renin allele (normal regulation of the RAS). The specific aims of the project are to: 1) utilize SS rats and novel narrowed congenic rat strains showing differential regulation of the renin-angiotensin system to test the hypothesis that chronic exposure to low levels of circulating ANG " contributes to impaired vascular relaxation in resistance arteries of normotensive SS rats maintained on NS diet;and 2), employ perturbations of circulating ANG " levels and pharmacological approaches such as angiotensin converting enzyme (ACE) inhibition and chronic AT1 receptor blockade to directly evaluate the role of physiological levels ANG " in maintaining normal vascular relaxation mechanisms in resistance arteries. These objectives will be accomplished by measuring vessel diameters and evaluating vessel responses to different endothelium-dependent vasodilator stimuli in SS rats and narrowed congenic rat strains either retaining the SS renin allele or carrying the normally functioning BN renin allele, which should restore normal regulation of the RAS and rescue normal vascular relaxation mechanisms in resistance arteries. These studies will not only enhance our understanding of the newly emerging role of ANG " in regulating vascular reactivity under normal physiological conditions, but will also provide valuable knowledge concerning the mechanisms of the impaired reactivity of resistance vessels to vasodilator stimuli in SS rats, and the potential mechanisms of elevated vascular resistance and increased cardiovascular mortality in human salt-sensitive hypertension.